Aim. To evaluate the effect of angiotensin II receptor blocker (ARB) therapy on the expression of transforming growth factor-β (TGF-β) in the myxomatous mitral valve, on the serum levels of TGF-β1/TGF-β2 and the left ventricular (LV) systolic function in patients with mitral valve prolapse (MVP).Material and methods. The retrospective non-randomized single-center study included 233 patients who underwent surgical treatment of severe mitral regurgitation due to MVP. Preoperative drug therapy was assessed using case records. Transthoracic echocardiography was performed in all patients before surgery. Pathological and immunohistochemical analysis of mitral valve fragments removed during surgery were performed. The serum content of TGF-β1 and TGF-β2 was determined by the enzyme immunoassay.Results. According to echocardiography, mitral valve leaflets were significantly longer and thicker in patients in the control group than in the ARB group. These data were confirmed by pathological study — most patients in the control group had excessive myxomatous mitral valve leaflets (χ2=7,9; p=0,005). In the ARB group, the expression of type III collagen in the mitral valve leaflets was lower compared to the control group and the expression of fibulin-5 did not differ. Also, in the main group, an increased density of valvular interstitial cells was found, including those expressing TGF-β1 and TGF-β2 compared to the control group. The serum level of TGF-β1 and TGF-β2 was significantly higher in the control group than in the ARB group.Despite the absence of differences in LV ejection fraction between the groups, global longitudinal systolic strain and strain rate were significantly higher in the main group.Conclusion. This is the first study to reveal a positive effect of ARB therapy on myxomatous mitral valve degeneration and LV function due to inhibition of the TGF-β signaling pathway, which opens up potential for pathogenetic therapy in patients with MVP.

Hypoplastic left heart syndrome (HLHS) is a common congenital heart defect, accounting for 4 to 16% of cases, and is one of the most prognostically unfavorable, involving single-­ventricle hemodynamics. HLHS involves hypoplasia of the left ventricle, often in combination with atresia and/or stenosis of the aortic and/or mitral valves, as well as hypoplasia of various parts of the aorta. Intrauterine reduction in blood flow to the left heart structures at early stages of fetal development subsequently leads to severe changes in cardiac structures, often not amenable to surgical correction. Objective. To study the clinical and morphological features of HLHS using a clinical case as an example. Materials and Methods. The patient was a child from the first pregnancy, which was complicated by anemia and first-­trimester preeclampsia. The defect was diagnosed prenatally at 23/24 weeks. At 39 weeks, labor was induced, and the infant was hospitalized in the intensive care unit with symptoms of cardiac and respiratory failure. On the 6th day of life, surgical treatment was performed — a Norwood operation, which is a single-­ventricle hemodynamic surgical correction of the defect. Despite intensive care measures, multiple organ failure progressed, leading to the development of disseminated intravascular coagulation (DIC) and subsequent death on the 10th day of life. Results. Autopsy, including staining of the myocardium with Masson’s trichrome and hematoxylin and eosin, showed pronounced plethora of the microcirculatory vessels with formation of erythrocyte thrombi. Pronounced perivascular edema and fraying of muscle fibers were detected. Fibroelastosis of the endocardium of the left ventricle was observed, characterized by pronounced sclerotic thickening due to significant proliferation of fibrous tissue, with the spread of connective tissue strands into the myocardium. Endocardial fibroelastosis is a component of HLHS and one of the determining factors in the outcome of cardiac surgery. Conclusion. The results of this work indicate the complexity of HLHS as a developmental defect, the severity of its clinical manifestations, and the limited prospects of currently existing surgical treatment methods. These patients may require heart transplantation in the first days of life. A potential alternative to early postnatal heart transplantation may be the development of methods for intrauterine correction of the existing developmental defect.

Mortality from myocardial infarction and its complications — heart rhythm disturbances, myocardial remodeling with subsequent development of congestive heart failure — occupies a leading place in the world. Activation of the epicardium is being actively studied as one of the ways to prevent cardiac remodeling. The method is based on the ability of embryonic epicardial cells to undergo epithelial-mesenchymal transformation, as a result of which the resulting epicardial-derived cells give rise to various cytological lines — cardiac fibroblasts, smooth muscle cells of the vascular wall, adipocytes and cardiomyocytes. In the postnatal period, this regenerative potential is absent. Currently, various methods have been developed to activate the reparative potential of the epicardium using options for genetic reprogramming of epicardial cells using viral vectors, exposure to paracrine factors involved in the formation of the heart and its structures — transcription factors GATA4, GATA6, thymosin-β4, introduction of embryonic stem cells or induced pluripotent stem cells in tissue-engineered constructs, activation of fibroblast growth factors ( FGF ), and platelet-derived growth factor ( PDGF ). These methods are being actively studied in experimental models of myocardial infarction and have shown their high efficiency in vitro. The results of transplantation of tissue-engineered structures during coronary artery bypass surgery in patients with severe post-infarction heart failure show promise in terms of slowing down myocardial remodeling.

Rosacea is a chronic inflammatory dermatosis characterized by facial skin lesions such as erythema, papules, pustules, phymas, and ocular involvement. In Russia, rosacea affects 5% of the population, while in European countries it ranges from 1.5% to 10%. This review presents the pathogenesis, classification, and modern approaches to the treatment of rosacea in Russia. Although rosacea is typically managed by specialists, it is also of interest to general practitioners. The goals of rosacea treatment are to reduce symptom severity and prevent disease exacerbations, thereby extending periods of stable remission. Despite advances in understanding the molecular mechanisms of the disease, development of classification approaches, and phenotype-­specific therapy, treatment failures and severe cases of rosacea persist. In addition to timely diagnosis and differential diagnosis in therapeutic practice, it is necessary to consider the increased risk of associations between rosacea and internal organ pathologies, as well as potential drug interactions among various medications used to treat this disease.

Objective. To evaluate morphological changes of placenta in 21 dead preterm babies with extremely low body weight. Materials and Methods. We evaluated the grade of immaturity of the placenta, inflammatory changes of placenta and extraplacental membranes in premature babies who died because of intraventricular hemorrhage (IVH) 2-3 grades and without sonographic and pathomorphological signs of IVH. Results. We identified the signs of ascending amniotic infections in 13 (100%) children with IVH and only in 4 (50%) babies without IVH. We also found that placenta damages in babies with IVH were associated with bacterial and mixed viral-bacterial infections, and the viral agent was represented mainly by the herpetic group. Only viral pathogens (mainly of the herpetic group) were identified as etiological factors of ascending infection in children without IVH. The role of compensatory changes of the placenta observed in children without signs of IVH in prolongation of pregnancy was noted. Conclusions. The presence of viral-bacterial lesions of placenta has a more pronounced impact on premature delivery, which increases the risk of complications in premature newborns in the form of damage to the central nervous system – intraventricular hemorrhages.

Bronchogenic cyst is a rare congenital anomaly of the formation of the pulmonary germ, a thin–walled formation filled with thick contents, which distinguishes it from aerial bronchial cysts. Clinically, a bronchogenic cyst can manifest itself as obstructive respiratory failure, swallowing disorders, and lead to recurrent purulent-­inflammatory processes. In this article, we present a clinical case of bronchogenic cyst in a newborn child, detected during pregnancy at the 2nd ultrasound screening and successfully operated on as planned. A 5-day-old boy was transferred to a surgical hospital for surgical treatment of cystic formation of the left lung S10 with dimensions 16.0×12.0×15.0 mm; the cyst contents were homogeneous, corresponding to the fluid. Surgical treatment was performed — the formation was separated from the parietal pleura and sent to the pathology department for histological examination. No complications were observed in the postoperative period. The macroscopically studied object was a three-­dimensional formation of gray-red color with a bluish tinge of irregular shape, dull, with a dark red fine sprinkling. A thin-walled cavity filled with cloudy jelly-like contents was determined on the incision. Microscopic description — a cyst lined with ciliated epithelium, partially flattened to cubic due to dystrophic changes, subepithelial islets of mature cartilage tissue and small groups of mucous glands. Thus, a bronchogenic cyst was morphologically verified. Differential diagnosis of bronchogenic cysts from inflammatory lung diseases (tuberculosis, abscess) with untimely diagnosis in the absence of clinical manifestations is practically impossible without histological examination. Therefore, prenatal diagnosis and morphological examination of the surgical material are crucial.

Cardiovascular diseases, and in particular, myocardial infarction, occupy a dominant place in the structure of mortality and disability worldwide. Long–term complications of a heart attack — myocardial remodeling, chronic heart failure, rhythm disturbances, left ventricular aneurysms significantly reduce the quality of life of patients, increase the level of disability, and finally, lead to serious financial costs. An urgent area of medicine is the search for mechanisms of cardiac regeneration after a myocardial infarction. The assumption about the regenerative potential of the epicardium is based on studying its properties and characteristics. During embryogenesis, the epicardium produces a large number of multipotent progenitor cells of the epicardium, which subsequently undergo epithelial-­mesenchymal transformation. These cells migrate into the thickness of the myocardium and give rise to various cardiac cell types, including cardiomyocytes. The epicardium participates in the synthesis of paracrine factors that ensure the growth of coronary vessels, as well as the differentiation and development of the myocardium as a whole. The mechanisms of myocardial repair being developed are based on various ways to stimulate the activity of the epicardium along the embryonic pathway. The article structures the currently available information on the reparative potential of the epicardium — physiological aspects in embryogenesis, as well as its response to myocardial damage.

Hypothyroidism is one of the most common endocrine disorders, occurring in at least 5% of the population. The clinical picture of hypothyroidism is often non-specific, and the only complaints of the patient may include muscular symptoms such as stiffness, myalgias, cramps and rapid fatigue. Differential diagnosis in such cases is difficult, requiring the exclusion of many diseases. Meanwhile, late detection of hypothyroidism can lead to complications affecting almost all systems of the body, primarily cardiovascular and nervous. Regarding the musculoskeletal system, hypothyroidism is dangerous due to the risk of rhabdomyolysis, Hoffmann’s syndrome and myasthenia gravis. Although the pathogenesis of hypothyroid myopathy is not fully understood, the presumed mechanisms of muscle tissue destruction are based on a decrease in the oxidative capacity of mitochondria and abnormal glycogenolysis, leading to several metabolic dysfunctions. The clinical and biochemical evaluation of hypothyroid myopathy was based on twenty-four cases described in the English-­language literature from 1975 to 2024. All subjects studied had an elevation of serum creatine phosphokinase (CK). This elevation does not necessarily correlate with the severity of myopathic symptoms and does not explain the cause of the presumed muscle damage. The obligatory clinical manifestation is muscle weakness. Other common clinical manifestations included slowed tendon reflexes with a slow relaxation phase, myalgia, cramps and muscle induration in the absence of muscle hypertrophy and stiffness. Clinical presentation alone is not sufficient to diagnose hypothyroid myopathy, so serum TSH levels should be evaluated in all patients with muscle weakness or elevated CK levels.

The review article discusses modern aspects of drug-induced liver injury (DILI) in patients with tuberculosis who are receiving etiotropic therapy. The main mechanisms of DILI, including toxic and idiosyncratic types, are described, as well as their pathogenetic, biochemical, and epidemiological differences. DILI can manifest as various clinicomorphological forms of liver damage, such as steatosis and steatohepatitis, acute and chronic hepatitis, mitochondrial cytopathy, cholestasis, sclerosing cholangitis, vascular injury, and others. The main diagnostic method for DILI is the detection of liver enzymes - transaminases and alkaline phosphatase - based on the degree of elevation and their ratio, which identify two main types of liver injury - hepatocellular and cholestatic - as well as a mixed variant. The article provides a scoring assessment of liver damage in a patient receiving chemotherapy to classify it as drug-induced liver injury.

Aim . To identify problems in the management of preventive examinations in remote areas, using the example of the Khvoininsky district of the Novgorod Oblast and ways to improve it. The article reveals the problems of managing preventive measures in the regions of the Russian Federation, remote from the regional center. Material and methods . Observations and experience of preventive measures carried out by the staff of St. Petersburg State Pediatric Medical University within the "University — Region" project, data from electronic medical records of 178 patients were used. Results . A high proportion of loss to follow-up was noted — 99 out of 278 (36%). The bulk was patients over 40 years old, who were assigned to health group IIIa. The difficulty of conducting medical examinations in a sparsely populated area is associated with insufficient awareness of the population, combined with low interest, a shortage of specialists, untimely necessary studies, a significant bureaucratic work, unstable Internet connection, and insufficient cancer awareness among medical workers. Conclusion . Expanding the promotion and information component of preventive measures, increasing patient focus, combining the first and second stages of clinical examination into one with subsequent convenient routing of patients, introducing telemedicine technologies and portable diagnostic complexes, improving the professional knowledge and competencies of primary care physicians — all these activities are aimed at improving coverage of population, increasing the adherence of patients with effective medical follow-up.

Adherence to treatment is understood as a complex model of the patient’s behavior in relation to their health, implemented in the degree of compliance of such behavior with respect to the recommendations received from the doctor regarding medications, self-control algorithms, diet and other lifestyle change measures. Adherence can be assessed by determining drug metabolites in body fluids (blood, urine) and using various questionnaires. At the same time, an important role in increasing adherence to therapy is assigned to the attending physician, without contact with which most patients make an independent decision to stop taking all or some of the prescribed drugs or to make an unreasonable correction of their dosages. Among the factors influencing the decrease in adherence to treatment of cardiac patients are the patient’s misunderstanding of their disease and the expected effects of therapy, fears of undesirable effects of therapy, a low level of motivation, a tendency towards forgetfulness and some others. Comorbidity and related polypharmacy also contribute to non-adherence, especially multiple drugs are prescribed simultaneously by various specialists — therapists, endocrinologists, urologists, neurologists, ophthalmologists. At the same time, there is a clear increase in undesirable consequences (repeated hospitalizations due to myocardial infarction and other cardiovascular events) in non-adherent patients 6 months after the previous coronary event and a significantly higher risk a year later. Increasing adherence to treatment is the task of medical workers, starting from the inpatient stage of treatment (clear recommendations noted in the discharge documents), followed by the support of outpatient doctors, explaining the need to take certain medications, and ending with monitoring the execution of medical prescriptions.

The review article presents modern concepts of the mitral valve prolapse. The issues of pathogenesis, diagnostic criteria of primary and probable prolapse are reflected, the issues of epidemiology are considered in detail. The problems associated with significant overdiagnosis of this condition in our country (up to 36.8%) are noted, which is due to ignoring internationally agreed algorithms and incorrect interpretation of the results obtained during echocardiography. When using a parasternal two-chamber position and choosing a diagnostic threshold of 3 mm or more, mitral valve prolapse is detected in 4.3% of practically healthy young people, which is comparable to population-based world studies, in the absence of sex differences. The place of mitral valve prolapse in the algorithms for diagnosing hereditary syndromes — Marfan and Ehlers-Danlos, its pleiotropy, which should be taken into account when stratifying the risk of clinically significant events and in case of probable prolapse, is discussed. The situations that allow to interpret mitral valve prolapse as an independent hereditary syndrome or a small anomaly of the heart are indicated. The article presents current views on the pathogenesis of mitral valve prolapse, the role of transforming growth factor-β in the progression of myxomatous degeneration of the valves, the development of manifestations of cardiomyopathy. The prognostic value of primary prolapse in its natural course is shown — the progression of myxomatosis of the valves, mitral insufficiency, dilation of the main vessels.

Introduction. Internet electrocardiography (internet-ECG) is becoming one of the most demanded areas of telemedicine; it becomes especially important in conditions of remoteness from medical and diagnostic institutions and impossibility of real consulting assistance of specialists. The general principle of operation of the internet-ECG devices is transferring the record to a server with subsequent processing and obtaining an automatic conclusion on the rhythm and morphology of the atrial-ventricular complex. At present, internet-ECG is widely used in adult network, while its possibilities in pediatrics are poorly covered. Materials and methods. The archive of children's ECGs recorded using the Cardiometer-MT system in the period from 2013 to 2021 has been analyzed. 3 groups of children were identified. 1st — screening of practically healthy children of primary school age (2153 children), 2nd group — school-age children examined in children's city polyclinics, who underwent stress and vegetative tests (2500 children), 3rd group — 200 healthy full-term newborn children who had a standard resting ECG on 1-2 days of life. Results. The advantages of using such systems in the mass examination of children of various ages in the framework of screening programs are shown. The results of an ECG examination of 2153 healthy children of primary school age are presented. The results of the automatic and medical conclusion are compared, sensitivity and specificity in the detection of cardiac arrhythmias and conduction are determined. The advantages of internet-ECG in carrying out vegetative and stress tests in the examination of adolescent children are substantiated. Performance of functional (including vegetative) and stress tests using internet-ECG systems allows to estimate reliably the functional state of the cardiovascular system, to determine adaptive capabilities of the vegetative nervous system, to reveal hypertension at early stages. Conclusion. The internet-ECG makes it possible to significantly simplify and streamline the ECG examination of children, forming an electronic archive of records, which is relevant for field examinations in children's groups and in conditions of a shortage of qualified specialists in functional diagnostics.

Kidney injury is a common pathology in the group of patients with systemic sclerosis. At least half of the patients show histological signs of it. Acute condition is known as scleroderma renal crisis. Although discussions regarding the risk factors for scleroderma renal crisis are open, most researchers consider the following factors: female sex, previous proteinuria and hypertension, the presence of anti-RNA polymerase III antibodies, and a decrease in lung diffusion capacity ≤75%. Diagnostic criteria for scleroderma renal crisis include an acute increase in blood pressure, accompanied by acute renal failure and abnormalities in the urinary sediment, anemia, and thrombocytopenia. Treatment of scleroderma renal crisis entails decreasing blood pressure, mainly with short-acting angiotensin-converting enzyme inhibitors, followed by selecting effective antihypertensive therapy. Further research of new treatment approaches is being carried on: the use of endothelin receptor antagonists (bosentan), monoclonal antibodies against the complement component 5 (eculizumab). Despite the approved strategies for identifying risk factors for scleroderma renal crisis development and treatment approaches, this group of patients is still characterized by high rates of mortality, the need for renal replacement therapy, and kidney transplantation. Thus, the problem of kidney injury in systemic sclerosis remains relevant.

Currently, hereditary connective tissue disorders (HCTD) are divided into hereditary syndromes - rare diseases that are diagnosed according to internationally agreed criteria (Marfan, Ehlers-Danlos, Stickler, Loeys-Dietz syndromes, and others), and a number of dysplastic phenotypes (marfanoid habitus, marfan-like and Ehlers-like phenotypes, benign joint hypermobility). The involvement of the bone system in the dysplastic process is typical for most HCTD. The bone signs of dysembriogenesis include malocclusion and dental growth disorders. The article presents an overview of current recommendations for a number of HCTD, assesses the role of facial signs of dysembriogenesis in the diagnostic algorithms for these diseases. A rather low prognostic value of such signs as malocclusion and dental growth disorders in the detection of hereditary syndromes and dysplastic phenotypes is shown. The clinical manifestations of HCTD in the maxillofacial region are analyzed - the frequent detection of different types of the malocclusion and dental growth disorders in HCTD is demonstrated. The difficulties of orthodontic treatment of patients with hereditary syndromes are substantiated.

The article presents an overview of modern approaches to the identification and justification of the choice of management tactics for patients with malocclusion and crowding of teeth. The questions of the etiology and pathogenesis of malocclusion that occurred both in early childhood and in older age are highlighted. There is a high prevalence of malocclusion in the population, which creates a number of medical problems (tooth erasability and mobility, changes in the upper-mandibular joint, abnormalities of the biomechanics of the lower jaw), but also a number of aesthetic and psychological problems. The classification of malocclusion anomalies is given. The article describes the currently relevant visualization methods for diagnosing malocclusion, which allow us to assess the severity of changes and adequately select the optimal method of correction, including orthopantomography and telerentgenography. The application of the calculation method is justified, which allows to establish the fact of a lack of space in the dental arch and to identify the need for its increase in case of crowding of teeth. Indications for extraction of teeth for correction of malocclusion have been determined. The factors determining the success of corrective treatment and the stability of the achieved results are listed.

Asthenic type of constitution and low body weight are traditionally associated with hereditary disorders (dysplasia) of connective tissue (HDCT). Another specific signs of HDCT is dolichostenomelia (skeletal imbalances). The prevalence of signs of dysembryogenesis and skeletal imbalances in young people depending on sex, type of constitution and body mass deficiency have not been previously assessed. Materials and methods. We examined 967 practically healthy people aged 18 to 25 years (330 boys and 637 girls) and 119 boys with a diagnosis of body weight deficiency by help general examination, phenotypic and anthropometric examinations. Results. Most bone signs of dysembryogenesis significantly often detected in young men: keel-shaped chest deformity (4% vs 1%, p 0.01) and funnel chest deformity (19% vs 9%, p 0.01) deformations of thorax, high palate (39% vs 28%, p 0.01), the growth of teeth (36% vs 19%, p 0.01) and dolichostenomelia. Girls are characterized by a high frequency of joint hypermobility (50% vs 24%) and atrophic striae (30% vs 14%, p 0.01). The bone signs (symptoms of arachnodactyly and chest deformities) detected more often in people with body weight deficiency, and the skin signs and joint hypermobility revealed more often in young people with normotrophy. Comparison of the frequency of signs of dysembryogenesis and skeletal imbalances in groups with asthenic and normal constitution did not reveal differences. All of external signs were found with equal frequency in individuals with different types of physique. Conclusions. Body weight deficiency in young men is closely related to bone signs of dysembryogenesis, while the asthenic type of constitution is not a reliable marker of connective tissue defect.

The paper presents a short survey of medical, research and educational activity of professor Zemtsovsky. Edward Veniaminovich Zemtsovsky is an avowed authority in our country in diagnostics and treatment of congenital connective tissue disorders. He has coauthored the first Russian recommendations for congenital connective tissue disorders diagnostics and treatment. Nowadays professor Zemtsovsky continues active research and pedagogical activity. He is a merited example of outstanding professional course of life.

For many hereditary connective tissue disorders (HCTD), especially Marfan syndrome, remodeling of the heart and main vessels is described, which is manifested by a decrease in the systolic function of the left ventricle and expansion of the thoracic aorta. Evaluation of morphometric characteristics of the heart and main vessels in patients with other HCTD, in particular marfanoid habitus (MH) has not been previously carried out. Materials and methods. Weexamined 90 young men and 74 young women between the ages of 18 to 25 years, 111 patients older age groups with stable over coronary heart disease (mean age 64.66.2 years) and 9 patients with verified Marfan syndrome (mean age 27.99.3years). All survey phenotypic and performed anthropometric survey identifying bone signs of dysembryogenesis as well as Echocardiography study on standard protocol. The results.Patients with MH as compared with control group revealed a relatively larger diameter of aortic root (30.44.7 vs 28.03.6 mm,p= 0.03) and the ascending aorta (26.64.9 vs 24.63.2 mm,p= 0.05). Also young with MH turned out to be significantly thicker myocardium of left ventricular posterior wall (8.30.8 vs 7.71.1 mm,p= 0.02) and interventricular septum (8.81.2vs 8.21.1mm,p= 0.04). When performing correlation analysis identified reliable positive correlation between such highly specialized bone signs as high palate (r= 0.31), infundibular deformation of the chest (r= 0.43), arachnodactyly (r= 0.45) andZ-test (p 0.05 for all). Expansion of the aorta (Z-criterion 2.0) have found 24% of older patients with MH. Conclusion.Inpatients with MH revealed significant structural changes of heart and main vessels which are progredient character thickening of the left ventricular myocardium and expansion of the aortic root.